Reducing Premature Coronary Artery Disease in Malaysia by Early Identification of Familial Hypercholesterolemia Using the Familial Hypercholesterolemia Case Ascertainment Tool (FAMCAT): Protocol for a Mixed Methods Evaluation Study
BackgroundFamilial hypercholesterolemia (FH) is predominantly caused by mutations in the 4 FH candidate genes (FHCGs), namely, low-density lipoprotein receptor (LDLR), apolipoprotein B-100 (APOB-100), proprotein convertase subtilisin/kexin type 9 (PCSK9), and the LDL receptor...
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| Format: | Article |
| Language: | English |
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JMIR Publications
2023-06-01
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| Series: | JMIR Research Protocols |
| Online Access: | https://www.researchprotocols.org/2023/1/e47911 |
| _version_ | 1797734089992699904 |
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| author | Anis Safura Ramli Nadeem Qureshi Hasidah Abdul-Hamid Aisyah Kamal Johanes Dedi Kanchau Nur Syahirah Shahuri Ralph Kwame Akyea Luisa Silva Laura Condon Suraya Abdul-Razak Alyaa Al-Khateeb Yung-An Chua Mohamed-Syarif Mohamed-Yassin Noorhida Baharudin Siti Fatimah Badlishah-Sham Aznida Firzah Abdul Aziz Noor Alicezah Mohd Kasim Siti Hamimah Sheikh Abdul Kadir Joe Kai Jo Leonardi-Bee Hapizah Nawawi |
| author_facet | Anis Safura Ramli Nadeem Qureshi Hasidah Abdul-Hamid Aisyah Kamal Johanes Dedi Kanchau Nur Syahirah Shahuri Ralph Kwame Akyea Luisa Silva Laura Condon Suraya Abdul-Razak Alyaa Al-Khateeb Yung-An Chua Mohamed-Syarif Mohamed-Yassin Noorhida Baharudin Siti Fatimah Badlishah-Sham Aznida Firzah Abdul Aziz Noor Alicezah Mohd Kasim Siti Hamimah Sheikh Abdul Kadir Joe Kai Jo Leonardi-Bee Hapizah Nawawi |
| author_sort | Anis Safura Ramli |
| collection | DOAJ |
| description |
BackgroundFamilial hypercholesterolemia (FH) is predominantly caused by mutations in the 4 FH candidate genes (FHCGs), namely, low-density lipoprotein receptor (LDLR), apolipoprotein B-100 (APOB-100), proprotein convertase subtilisin/kexin type 9 (PCSK9), and the LDL receptor adaptor protein 1 (LDLRAP1). It is characterized by elevated low-density lipoprotein cholesterol (LDL-c) levels leading to premature coronary artery disease. FH can be clinically diagnosed using established clinical criteria, namely, Simon Broome (SB) and Dutch Lipid Clinic Criteria (DLCC), and can be identified using the Familial Hypercholesterolemia Case Ascertainment Tool (FAMCAT), a primary care screening tool.
ObjectiveThis study aims to (1) compare the detection rate of genetically confirmed FH and diagnostic accuracy between the FAMCAT, SB, and DLCC in the Malaysian primary care setting; (2) identify the genetic mutation profiles, including novel variants, in individuals with suspected FH in primary care; (3) explore the experience, concern, and expectation of individuals with suspected FH who have undergone genetic testing in primary care; and (4) evaluate the clinical utility of a web-based FH Identification Tool that includes the FAMCAT, SB, and DLCC in the Malaysian primary care setting.
MethodsThis is a mixed methods evaluation study conducted in 11 Ministry of Health primary care clinics located at the central administrative region of Malaysia. In Work stream 1, the diagnostic accuracy study design is used to compare the detection rate and diagnostic accuracy of the FAMCAT, SB, and DLCC against molecular diagnosis as the gold standard. In Work stream 2, the targeted next-generation sequencing of the 4 FHCGs is used to identify the genetic mutation profiles among individuals with suspected FH. In Work stream 3a, a qualitative semistructured interview methodology is used to explore the experience, concern, and expectation of individuals with suspected FH who have undergone genetic testing. Lastly, in Work stream 3b, a qualitative real-time observation of primary care physicians using the “think-aloud” methodology is applied to evaluate the clinical utility of a web-based FH Identification Tool.
ResultsThe recruitment for Work stream 1, and blood sampling and genetic analysis for Work stream 2 were completed in February 2023. Data collection for Work stream 3 was completed in March 2023. Data analysis for Work streams 1, 2, 3a, and 3b is projected to be completed by June 2023, with the results of this study anticipated to be published by December 2023.
ConclusionsThis study will provide evidence on which clinical diagnostic criterion is the best to detect FH in the Malaysian primary care setting. The full spectrum of genetic mutations in the FHCGs including novel pathogenic variants will be identified. Patients’ perspectives while undergoing genetic testing and the primary care physicians experience in utilizing the web-based tool will be established. These findings will have tremendous impact on the management of patients with FH in primary care and subsequently reduce their risk of premature coronary artery disease.
International Registered Report Identifier (IRRID)DERR1-10.2196/47911 |
| first_indexed | 2024-03-12T12:38:16Z |
| format | Article |
| id | doaj.art-4814feb6ccc04477a58584b9c2f3fcf7 |
| institution | Directory Open Access Journal |
| issn | 1929-0748 |
| language | English |
| last_indexed | 2024-03-12T12:38:16Z |
| publishDate | 2023-06-01 |
| publisher | JMIR Publications |
| record_format | Article |
| series | JMIR Research Protocols |
| spelling | doaj.art-4814feb6ccc04477a58584b9c2f3fcf72023-08-29T00:00:16ZengJMIR PublicationsJMIR Research Protocols1929-07482023-06-0112e4791110.2196/47911Reducing Premature Coronary Artery Disease in Malaysia by Early Identification of Familial Hypercholesterolemia Using the Familial Hypercholesterolemia Case Ascertainment Tool (FAMCAT): Protocol for a Mixed Methods Evaluation StudyAnis Safura Ramlihttps://orcid.org/0000-0002-9517-1413Nadeem Qureshihttps://orcid.org/0000-0003-4909-0644Hasidah Abdul-Hamidhttps://orcid.org/0000-0002-1642-0427Aisyah Kamalhttps://orcid.org/0009-0001-2719-5659Johanes Dedi Kanchauhttps://orcid.org/0009-0008-2100-8040Nur Syahirah Shahurihttps://orcid.org/0009-0003-6934-4055Ralph Kwame Akyeahttps://orcid.org/0000-0003-4529-8237Luisa Silvahttps://orcid.org/0000-0003-4884-6657Laura Condonhttps://orcid.org/0000-0002-7039-3095Suraya Abdul-Razakhttps://orcid.org/0000-0001-5376-2509Alyaa Al-Khateebhttps://orcid.org/0000-0002-4263-2191Yung-An Chuahttps://orcid.org/0000-0003-2387-0087Mohamed-Syarif Mohamed-Yassinhttps://orcid.org/0000-0003-3654-2146Noorhida Baharudinhttps://orcid.org/0000-0002-8188-4148Siti Fatimah Badlishah-Shamhttps://orcid.org/0000-0003-3001-7447Aznida Firzah Abdul Azizhttps://orcid.org/0000-0001-7620-4008Noor Alicezah Mohd Kasimhttps://orcid.org/0000-0003-3855-5768Siti Hamimah Sheikh Abdul Kadirhttps://orcid.org/0000-0002-1671-4839Joe Kaihttps://orcid.org/0000-0001-9040-9384Jo Leonardi-Beehttps://orcid.org/0000-0003-0893-6068Hapizah Nawawihttps://orcid.org/0000-0003-4462-8484 BackgroundFamilial hypercholesterolemia (FH) is predominantly caused by mutations in the 4 FH candidate genes (FHCGs), namely, low-density lipoprotein receptor (LDLR), apolipoprotein B-100 (APOB-100), proprotein convertase subtilisin/kexin type 9 (PCSK9), and the LDL receptor adaptor protein 1 (LDLRAP1). It is characterized by elevated low-density lipoprotein cholesterol (LDL-c) levels leading to premature coronary artery disease. FH can be clinically diagnosed using established clinical criteria, namely, Simon Broome (SB) and Dutch Lipid Clinic Criteria (DLCC), and can be identified using the Familial Hypercholesterolemia Case Ascertainment Tool (FAMCAT), a primary care screening tool. ObjectiveThis study aims to (1) compare the detection rate of genetically confirmed FH and diagnostic accuracy between the FAMCAT, SB, and DLCC in the Malaysian primary care setting; (2) identify the genetic mutation profiles, including novel variants, in individuals with suspected FH in primary care; (3) explore the experience, concern, and expectation of individuals with suspected FH who have undergone genetic testing in primary care; and (4) evaluate the clinical utility of a web-based FH Identification Tool that includes the FAMCAT, SB, and DLCC in the Malaysian primary care setting. MethodsThis is a mixed methods evaluation study conducted in 11 Ministry of Health primary care clinics located at the central administrative region of Malaysia. In Work stream 1, the diagnostic accuracy study design is used to compare the detection rate and diagnostic accuracy of the FAMCAT, SB, and DLCC against molecular diagnosis as the gold standard. In Work stream 2, the targeted next-generation sequencing of the 4 FHCGs is used to identify the genetic mutation profiles among individuals with suspected FH. In Work stream 3a, a qualitative semistructured interview methodology is used to explore the experience, concern, and expectation of individuals with suspected FH who have undergone genetic testing. Lastly, in Work stream 3b, a qualitative real-time observation of primary care physicians using the “think-aloud” methodology is applied to evaluate the clinical utility of a web-based FH Identification Tool. ResultsThe recruitment for Work stream 1, and blood sampling and genetic analysis for Work stream 2 were completed in February 2023. Data collection for Work stream 3 was completed in March 2023. Data analysis for Work streams 1, 2, 3a, and 3b is projected to be completed by June 2023, with the results of this study anticipated to be published by December 2023. ConclusionsThis study will provide evidence on which clinical diagnostic criterion is the best to detect FH in the Malaysian primary care setting. The full spectrum of genetic mutations in the FHCGs including novel pathogenic variants will be identified. Patients’ perspectives while undergoing genetic testing and the primary care physicians experience in utilizing the web-based tool will be established. These findings will have tremendous impact on the management of patients with FH in primary care and subsequently reduce their risk of premature coronary artery disease. International Registered Report Identifier (IRRID)DERR1-10.2196/47911https://www.researchprotocols.org/2023/1/e47911 |
| spellingShingle | Anis Safura Ramli Nadeem Qureshi Hasidah Abdul-Hamid Aisyah Kamal Johanes Dedi Kanchau Nur Syahirah Shahuri Ralph Kwame Akyea Luisa Silva Laura Condon Suraya Abdul-Razak Alyaa Al-Khateeb Yung-An Chua Mohamed-Syarif Mohamed-Yassin Noorhida Baharudin Siti Fatimah Badlishah-Sham Aznida Firzah Abdul Aziz Noor Alicezah Mohd Kasim Siti Hamimah Sheikh Abdul Kadir Joe Kai Jo Leonardi-Bee Hapizah Nawawi Reducing Premature Coronary Artery Disease in Malaysia by Early Identification of Familial Hypercholesterolemia Using the Familial Hypercholesterolemia Case Ascertainment Tool (FAMCAT): Protocol for a Mixed Methods Evaluation Study JMIR Research Protocols |
| title | Reducing Premature Coronary Artery Disease in Malaysia by Early Identification of Familial Hypercholesterolemia Using the Familial Hypercholesterolemia Case Ascertainment Tool (FAMCAT): Protocol for a Mixed Methods Evaluation Study |
| title_full | Reducing Premature Coronary Artery Disease in Malaysia by Early Identification of Familial Hypercholesterolemia Using the Familial Hypercholesterolemia Case Ascertainment Tool (FAMCAT): Protocol for a Mixed Methods Evaluation Study |
| title_fullStr | Reducing Premature Coronary Artery Disease in Malaysia by Early Identification of Familial Hypercholesterolemia Using the Familial Hypercholesterolemia Case Ascertainment Tool (FAMCAT): Protocol for a Mixed Methods Evaluation Study |
| title_full_unstemmed | Reducing Premature Coronary Artery Disease in Malaysia by Early Identification of Familial Hypercholesterolemia Using the Familial Hypercholesterolemia Case Ascertainment Tool (FAMCAT): Protocol for a Mixed Methods Evaluation Study |
| title_short | Reducing Premature Coronary Artery Disease in Malaysia by Early Identification of Familial Hypercholesterolemia Using the Familial Hypercholesterolemia Case Ascertainment Tool (FAMCAT): Protocol for a Mixed Methods Evaluation Study |
| title_sort | reducing premature coronary artery disease in malaysia by early identification of familial hypercholesterolemia using the familial hypercholesterolemia case ascertainment tool famcat protocol for a mixed methods evaluation study |
| url | https://www.researchprotocols.org/2023/1/e47911 |
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